Nanoparticle-containing placental constructs and methods of use

ABSTRACT

A placental construct is provided. The placental construct includes a therapeutically effective amount of human birth tissue material and a nanoparticle composition. Methods of treatment with the placental construct and a corresponding kit are also provided.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application is a continuation of U.S. application Ser. No.14/988,841 filed Jan. 6, 2016, which claims priority to U.S. ProvisionalApplication No. 62/100,204 filed Jan. 6, 2015, the entirety of each isincorporated herein by reference.

BACKGROUND OF THE INVENTION

Human placental tissue has been used in various surgical procedures,including skin transplantation and ocular surface disorders, for over acentury. The tissue has been shown to provide good wound protection,prevent surgical adhesions, reduce pain, reduce wound dehydration, andprovide anti-inflammatory and anti-microbial effects.

The placenta is a fetomaternal organ consisting of a placental globe,umbilical cord, associated membranes (chorionic membrane and amnioticmembrane), other gelatins, fluids, cells and extracellular material. Thechorionic membrane and the amniotic membrane are attached by looseconnective tissue and make up the placental sac. The innermost membraneof the placental sac is the amniotic membrane, which comes into contactwith the amniotic fluid that surrounds the fetus. The amniotic membraneis avascular and lined by simple columnar epithelium overlying a basalmembrane. The chorionic membrane is the outermost layer of the sac andis heavily cellularized. The placental membranes have an abundant sourceof collagen that provides an extracellular matrix to act as a naturalscaffold for cellular attachment in the body. Collagen provides astructural tissue matrix that facilitates, among other things, cellmigration and proliferation in vivo.

While human placental tissue exhibits the aforementioned advantageousproperties, there still remains a need for a placental construct thatnot only aids in the healing cascade but also is capable of providingantimicrobial, antiviral, antifungal, angiogenic, neurogenic,collagenic, and osteogenic properties or any combination thereof.

SUMMARY OF THE INVENTION

A placental construct is provided that includes a therapeuticallyeffective amount of human birth tissue material and a nanoparticlecomposition. According to one embodiment, the birth tissue materialincludes one or more components of a human placental organ including theplacental globe, the umbilical cord, the chorionic membrane, theamniotic membrane, and amniotic fluid. According to one embodiment, theplacental construct is formulated as a flowable, injectable semi-solid,a single layer graft, or a multi-layer graft. According to oneembodiment, the nanoparticle composition includes one or more elementalnanoparticles. Suitable elemental nanoparticles include, but are notlimited to, silver, gold, magnesium, copper, aluminum, titanium, indium,cobalt, nickel, silicon, zirconium, samarium, lanthanum, and zinc.According to another embodiment, the nanoparticle composition includesone or more nanoparticles that are elemental ions. Suitable elementalions include, but are not limited to, silver, gold, magnesium, copper,aluminum, titanium, indium, cobalt, nickel, silicon, zirconium,samarium, lanthanum, and zinc ions. The nanoparticle composition mayinclude oxides of the elements provided herein (e.g., TiO₂). Accordingto one embodiment, the nanoparticle composition may include one or moreimpurities including osmium, rhenium, rhodium, tin, platinum, lithium,sodium, silver, zinc, silicon, carbon, nitrogen, sulfur, iron,moldybdenum, rubidium, copper, and potassium. According to oneembodiment, the nanoparticle composition is dispersed within the humanbirth tissue material, applied to an inside surface of the resultingplacental construct, or applied to an outside surface of the construct.According to one embodiment, the placental construct exhibitsantimicrobial, antiviral, antifungal, angiogenic, neurogenic,collagenic, and osteogenic properties or any combination thereof.According to one embodiment, the placental construct further comprisesamniotic fluid, amniotic fluid components, or a combination thereof.According to one embodiment, the human birth tissue material iscellularized (i.e., not manipulated in any way to decellularize orremove cells or cellular components).

According to another aspect, a method of treating a skin condition orsoft tissue defect of the skin is provided. The method includes the stepof applying an effective amount of the placental construct to the skincondition or soft tissue defect of the skin. According to oneembodiment, the skin condition is an ischemic wound, scar, traumaticwound, severe burn, or surgical wound. According to one embodiment, theskin condition is keratosis, melasma, pruritus, spider veins, lentigo,dermatitis, psoriasis, folliculitis, rosacea, impetigo, erysipelas,erythrasma, or eczema.

According to another aspect, a method of treating a bone defect isprovided. The method includes the step of administering an effectiveamount of the placental construct to the bone defect. According to oneembodiment, the placental construct aids in bone regeneration.

According to another aspect, a method of preventing or killing apathological infection at a site on or within the body is provided. Themethod includes the step of administering an effective amount of theplacental construct to the site. According to one embodiment, theplacental construct includes a nanoparticle composition that includesmagnesium ions.

According to another aspect, a kit is provided that includes a placentalconstruct as provided herein. The kit may further include a set ofinstructions for use thereof.

DETAILED DESCRIPTION OF THE INVENTION

The present disclosure will now be described more fully hereinafter withreference to exemplary embodiments thereof. These exemplary embodimentsare described so that this disclosure will be thorough and complete, andwill fully convey the scope of the disclosure to those skilled in theart. Indeed, the present disclosure may be embodied in many differentforms and should not be construed as limited to the embodiments setforth herein; rather, these embodiments are provided so that thisdisclosure will satisfy applicable legal requirements. As used in thespecification, and in the appended claims, the singular forms “a”, “an”,“the”, include plural referents unless the context clearly dictatesotherwise.

As used herein, the term “nanoparticle” encompasses particles having onedimension that is less than about 100 nanometers in size.

As used herein, the term “nanoparticle composition” refers to anysubstance that contains at least one nanoparticle.

As used herein, “human birth tissue” encompasses one or more of thecomponents of the placental organ including, but not limited to, theplacental globe, the umbilical cord, the umbilical cord blood, thechorionic membrane, the amniotic membrane, the Wharton's jelly, othergelatins, cells, and extracellular material, and the amniotic fluid.

As used herein, “placental tissue components” encompasses one or more ofthe tissue components of the placental organ including, but not limitedto, the placental globe, the umbilical cord, the umbilical cord blood,the chorionic membrane, the amniotic membrane, the Wharton's jelly andother gelatins, cells and extracellular material.

As used herein, the term “amnion” and “amniotic membrane” are usedinterchangeably.

As used herein, the term “cellularized” refers to a tissue that is notmanipulated in any way to decellularize or remove cells or cellularcomponents.

A placental construct is provided. The placental construct includeshuman birth tissue and at least one nanoparticle composition. The humanbirth tissue can be prepared according to the steps provided herein andcombined with the nanoparticle composition to formulate a placentalconstruct that exhibits antimicrobial, antiviral, antifungal,angiogenic, neurogenic, collagenic, osteogenic properties or anycombination thereof. The placental construct is effective at preventingor killing pathological infection and promoting tissue and bone repairand regeneration.

According to one embodiment, the placental construct provided herein maybe used to promote bone regeneration which is aided, in part, by theosteogenic properties of the nanoparticle composition. According to oneembodiment, the placental construct provided herein exhibits increasedmechanical strength for bone grafting purposes. According to oneembodiment, the placental construct provided herein is capable ofsupporting osteogenic cell growth and differentiation. According to aparticular embodiment, the placental construct provided herein aids inthe sterilization and prevention of microbial growth at the site of useupon administration. According to a particular embodiment, thenanoparticle composition included in or on the placental construct aidsin the sterilization of the construct. According to a particularembodiment, the nanoparticle composition included in or on the placentalconstruct aids in preventing or reducing infection at a site where theplacental construct may be placed on or within the body.

According to one embodiment, the placental construct as provided hereinmay be formulated in a variety of manners that are suitable forpreventing or killing pathological infection and promoting tissue andbone repair and regeneration. According to one embodiment, the placentalconstruct as provided herein may be formulated for any route ofadministration, including, but not limited to, oral (PO), intravenous(IV), intramuscular (IM), intra-arterial, intramedullary, intrathecal,subcutaneous (SQ), intraventricular, transdermal, interdermal,intradermal, rectal (PR), vaginal, intraperitoneal (IP), intragastric(IG), topical and/or transdermal (e.g., by lotions, creams, powders,ointments, liniments, gels, drops, etc.), mucosal, intranasal, buccal,enteral, vitreal, and/or sublingual administration. According to aparticular embodiment, the placental construct is formulated as aflowable, injectable semi-solid. According to another embodiment, theplacental construct as provided herein is formulated as a single ormulti-layered graft. The placental construct as provided herein issuitable for application onto or into any part of the body.

To prepare the human birth tissue material for inclusion in a placentalconstruct, placental tissue components and amniotic fluid are initiallyrecovered from a seronegative, healthy human. Potential human birthtissue donors providing informed consent are pre-screened during anexamination of pre-natal medical records and blood test results. Acomprehensive medical history and behavior risk assessment is obtainedfrom the donor prior to donation incorporating U.S. Public HealthService guidelines. Discussions with the physician(s) and/or the donormother are conducted to identify circumstances that may lead to theexclusion of the donor or donated tissue. Additionally, a physical examis performed on the donor to determine whether there is evidence of highrisk behavior or infection and to determine the overall general healthof the donor.

Infectious disease testing of donor blood specimens is performed foreach tissue donor on a specimen collected at the time of donation orwithin seven days prior to or after donation. Advantageously, themethods that are used to screen for a communicable disease follow theregulations as set forth by the Federal Drug Administration and theAmerican Association of Tissue Banks. Exemplary infectious diseasetesting includes, but is not limited to, antibodies to the humanimmunodeficiency virus, type 1 and type 2 (anti-HIV-1 and anti-HIV-2);nucleic acid test (NAT) for HIV-1; hepatitis B surface antigen (HBsAg);total antibodies to hepatitis B core antigen (anti-HBc—total, meaningIgG and IgM); antibodies to the hepatitis C virus (anti-HCV); NAT forHCV; antibodies to human T-lymphotropic virus type I and type II(anti-HTLV-I and anti-HTLV-II); and syphilis (a non-treponemal ortreponemal-specific assay may be performed).

Human birth tissue is preferably recovered from a full-term Cesareandelivery of a newborn. Alternatively, human birth tissue is recoveredfrom a full-term vaginal delivery of a newborn. The subsequent steps ofpreparing the human birth tissue material are performed in a controlledenvironment (i.e., certified biological safety cabinet, hood or cleanroom). Instruments, solutions, and supplies coming into contact with thehuman birth tissue material during processing are sterile. All surfacescoming in contact with the human birth tissue material intended fortransplant are either sterile or draped using aseptic technique.

According to one embodiment, the placental tissue components include oneor more components selected from the group consisting of amnioticmembrane, chorionic membrane, Wharton's jelly, umbilical cord tissue,umbilical cord blood, placental globe, and other gelatins, other cellsand extracellular matrix from placental tissue components. Othervariations of the invention include, however, removing one or more ofthe placental globe, umbilical cord tissue, umbilical cord blood,chorionic membrane, amniotic membrane, or Wharton's jelly before furtherprocessing. Removal of one or more of the placental tissue componentscan be achieved via a sterile saline solution rinse, blunt dissection,scalpel, or a combination thereof, if necessary. According to oneembodiment, the human birth tissue material is cellularized (i.e., notmanipulated in any way to decellularize or remove cells or cellularcomponents).

The retained placental tissue components can be placed in a steriletransport solution after aseptic recovery. The sterile transportsolution is used to provide an advantageous medium to the naturalfunction of tissue components prior to processing. Throughout thepreparation of the human birth tissue material, various methods can beused to drive undifferentiated cells to differentiate into specializedcell types including, but not limited to, transport solutions, soaks,particular temperature ranges, and hyperbaric pressure.

The sterile transport solution preferably includes sodium chloride(NaCl) in a concentration range from typically about 10% to typicallyabout 20% by weight. The sterile transport solution can also include oneor more of Minimum Essential Medium, Dulbecco's Modified Eagle's Medium,Plasma Lyte-A, human albumin 25% solution, calcium-rich water, alkalineionized water, or acidic ionized water.

Optionally, the placental tissue components may be soaked in a sterilesaline solution for one or more soaks to remove all maternal components.In one embodiment, the sterile saline solution includes NaCl in aconcentration range from typically about 10% to typically about 15% byweight.

Optionally, the placental tissue components can be cryopreservedaccording to methods commonly used in the art. The placental tissuecomponents can be soaked in cryoprotectant prior to cryopreservation. Inone embodiment, the cryoprotectant is one commonly used in the industry,such as, for example, dimethyl sulfoxide (DMSO). In a preferredembodiment, the cryoprotectant is an amnion control rate freeze solutioncomprising typically about 44% volume of Plasma Lyte-A, typically about36% volume of human albumin 25% solution, and typically about 20% volumeof dimethyl sulfoxide. In another embodiment, the cryoprotectant is acommercially available cryoprotectant such as Synth-a-Freeze® availablefrom Invitrogen. Any cryoprotectant specific to the birth tissuematerial described herein may be used. In one embodiment,cryopreservation is achieved using a controlled rate freezer, resultingin a 1° C. rate from nucleation to −35° C. and a 10° C. per minutecooling rate to a −90° C. end temperature. However, any cryopreservationmethod commonly known in the art may be used.

The birth tissue material can be subjected to morselization. As usedherein, “morselization” means to grind up to particle form. According toone embodiment, the morselized human birth tissue material renders theresulting placental construct flowable. According to one embodiment, themorselized human birth tissue material renders the resulting placentalconstruct injectable. According to one embodiment, the morselized humanbirth tissue material renders the resulting placental construct able toconform to a particular area of treatment.

Tissue morselization may occur by any art-recognized method of tissuedisruption, including, but not limited to: milling, blending,sonicating, homogenizing, micronizing, pulverizing, macerating, handpressing, or a combination thereof. In one embodiment, the placentaltissue components are subjected to cryogenic milling by methods commonlyknown in the art. In a preferred embodiment, the tissue is cryogenicallymilled in a CryoMill® (available from Retsch) for two cycles at afrequency 1/s of 25 Hz with a pre-cooling time of no more than aboutfive minutes, a grinding time of no more than about two minutes, and anintermediate cooling time of no more than about five minutes. In anotherembodiment, a Freezer/Mill® available from SPEX SamplePrep, LLC may beused. After morselization, the milled human birth tissue material can beretained and preserved until combined with the carrier composition asdescribed herein to formulate the final placental construct.

In one embodiment, the tissue may be morselized or otherwise renderedinto fine particulates. Particles may be micron or submicron sizeranges. In one embodiment, particle sizes may range from 1 micron to 100microns. In another embodiment, particle sizes may range from 10 nm to100 nm. Particles must be of sufficient size to allow diffusion throughskin.

The resulting human birth tissue as provided herein may then be combinedwith a nanoparticle composition as provided herein to yield a placentalconstruct. The nanoparticle composition may be dispersed within thehuman birth tissue material or applied to an inside surface or anoutside surface of the construct (e.g., a graft). According to oneembodiment, the nanoparticle composition is mixed or admixed with thehuman birth tissue as provided herein. According to one embodiment, thenanoparticle composition is mixed or admixed with the human birth tissuematerial as provided herein but no crosslinking is achieved between thenanoparticle composition and the human birth tissue material. Accordingto one embodiment, the nanoparticle composition does not bond to or bondwith the human birth tissue material as provided herein. Thenanoparticle composition may include various components which may varyaccording to the end formulation and end use. The nanoparticlecomposition may include one or more nanoparticles or nanoparticlecomplexes that exhibit antimicrobial, antiviral, antifungal, angiogenic,neurogenic, collagenic, osteogenic properties or any combinationthereof.

According to one embodiment, the nanoparticle composition includes oneor more elemental nanoparticles. Suitable elemental nanoparticlesinclude, but are not limited to, silver, gold, magnesium, copper,aluminum, titanium, indium, cobalt, nickel, silicon, zirconium,samarium, lanthanum, and zinc. According to another embodiment, thenanoparticle composition includes one or more nanoparticles that areelemental ions. Suitable elemental ions include, but are not limited to,silver, gold, magnesium, copper, aluminum, titanium, indium, cobalt,nickel, silicon, zirconium, samarium, lanthanum, and zinc ions. Thenanoparticle composition may include oxides of the elements providedherein (e.g., TiO₂). According to one embodiment, the nanoparticlecomposition may further include a biocompatible drug, growth factor,and/or bioactive agent. Suitable bioactive agents include, but are notlimited to, physiologically compatible minerals, growth factors,antibiotics, chemotherapeutic agents, antigen, antibodies, enzymes,vectors for gene delivery and hormones may also be added to thenanoparticle composition. According to one embodiment, the nanoparticlecomposition may further include a biocompatible polymer.

According to one embodiment, the nanoparticle composition may includeone or more impurities (e.g., dopant, doping agent) that are introducedfor the purpose of modifying the properties of the nanoparticlecomposition. Suitable impurities include osmium, rhenium, rhodium, tin,platinum, lithium, sodium, silver, zinc, silocon, carbon, nitrogen,sulfur, iron, moldybdenum, rubidium, copper, and potassium.

According to one embodiment, the nanoparticle composition may includeone or more pharmaceutically acceptable excipients. Optionally, asuitable amount of amniotic fluid components may also be combined withthe nanoparticle composition.

For topical applications, the placental construct may further include acarrier composition. The carrier composition can include any variety ofcomponents suitable for application to the human skin. According to oneembodiment, the carrier composition includes one or more vitamins,minerals, proteins, fats, collagens (including collagen extracted fromthe placental globe), waxes, glycols and derivatives thereof, glyercolsand derivatives thereof, oils (including essential oils), skin-abradinggranules, fatty acids, cholesterols, alcohols, emollients, adsorbents,lubricants, moisturizing agents, emulsifying agents, thickening agents,humectants, surfactants, pharmaceutical ingredients, preservatives,antifungal agents, antioxidants, antimicrobial agents, structuringagents, dispersing agents, UV blocker and absorber ingredients(sunscreen), pH-adjusting components, sequestering or chelating agents,wetting agents and other components known in the art to be suitable foruse in a placental construct.

The carrier composition can include other suitable components including,but not limited to, water, retinol, sorbitol, lanolin, beeswax, oleicacid, spermaceti, almond oil, egg oil, aloe, castor oil, tracacanth gum,clay, magnesia, talc, metal stearates, chalk, magnesium carbonate, zincstearate, kaolin, glycerin, propylene glycol, polyethylene glycol,hyaluronic acid, chondroitin sulfate, elastin, polysaccharide,glycosaminoglycan, ascorbic acid, ascorbic acid derivatives, glucosamineascorbate, arginine ascorbate, lysine or tyrosine ascorbate,gluthathione ascorbate, nicotinamide ascorbate, niacin ascorbate,allantoin ascorbate, creatine ascorbate, creatinine ascorbate,chondroitin ascorbate, chitosan ascorbate, DNA ascorbate, alpha hydroxylacids, carnosine ascorbate, tocotrienol, rutin, quercetin, hesperedin,diosmin, mangiferin, mangostin, cyanidin, astaxanthin, lutein, lycopene,resveratrol, tetrahydrocurcumin, rosmarinic acid, hypericin, ellagicacid, chlorogenic acid, oleuropein, alpha-lipoic acid, niacinamidelipoate, gluthathione, andrographolide, carnosine, niacinamide,polyphenols, pycnogenol and mixtures thereof, benzophenones,benzotriazoles, homosalates, alkyl cinnamates, salicylates such as octylsalicylate, dibenzoylmethanes, anthranilates, methylbenzylidenes, octyltriazones, 2-phenylbenzimidazole-5-sulfonic acid, octocrylene,triazines, cinnamates, cyanoacrylates, dicyano ethylenes, etocrilene,drometrizole trisiloxane, bisethylhexyloxyphenol methoxyphenol triazine,drometrizole, dioctyl butamido triazone, terephthalylidene dicamphorsulfonic acid and para-aminobenzoates as well as ester derivativesthereof; antiacne agents such as salicylic acid; skin bronzing ortanning agent ingredients such as dihydroxyacetone, erytrulose, melanin;antioxidants such as vitamin C and derivatives thereof (e.g. ascorbylacetate, ascorbyl phosphate and ascorbyl palmitate), vitamin A andderivatives thereof; folic acid and derivatives thereof; vitamin E andderivatives thereof such as tocopheryl acetate, flavons, or flavonoids,amino acids such as histidine, glycine, tyrosine, tryptophan, andderivatives thereof; carotenoids and carotenes; uric acid andderivatives thereof; citric acid, lactic acid, malic acid; stilbenes andderivatives thereof; and pomegranate extracts; vitamin K1 or K2, vitaminK1 oxide or vitamin K2 oxide, hormones, plant or botanical extracts,anti-inflammatory agents, concentrates of plant extracts, silicones,skin soothing ingredients, analgesics or anti-itch agents, skinpenetration enhancers, solubilizers, alkaloids and processing aids;coloring agents including various dyes and pigments; perfumes orfragrances for the body; and other suitable components that do notinterfere with the interaction between the birth tissue material and thevarious layers of the human skin.

The carrier composition is formulated in such a way that the combinationof the birth tissue material and carrier composition are chemicallycompatible and do not form complexes which precipitate from the finalplacental construct. According to one embodiment, the carriercomposition can be formulated as a cream, emulsion, lotion, gel,ointment, salve, butter, gel, putty, or balm. According to a preferredembodiment, the carrier composition is a cream.

The amount of human birth tissue material present in the placentalconstruct can vary depending upon the location and purpose of use, thefrequency of use, and the severity of the defect or condition to betreated. According to one embodiment, the placental construct includes atherapeutically effective amount of birth tissue material. According toone embodiment, the placental construct includes from typically about0.1% to about 99.0% birth tissue material based on total placentalconstruct weight. According to one embodiment, the placental constructincludes from typically about 0.1% to about 99.0% of a nanoparticlecomposition as provided herein based on total placental constructweight.

Also provided herein is a kit that includes a placental construct asdescribed herein. Such kits can include a package that is adapted toreceive one or more containers, each of the container(s) including aplacental construct as described herein. The kit is appropriatelypreserved up until and during shipment to a distributor or medicalfacility. The kit additionally includes at least one set of instructionsfor the end user including an explanation of how to apply, use, andmaintain the placental construct.

Although specific embodiments of the present invention are hereinillustrated and described in detail, the invention is not limitedthereto. The above detailed descriptions are provided as exemplary ofthe present invention and should not be construed as constituting anylimitation of the invention. Modifications will be obvious to thoseskilled in the art, and all modifications that do not depart from thespirit of the invention are intended to be included with the scope ofthe appended claims.

I claim:
 1. A placental construct comprising: a therapeuticallyeffective amount of human birth tissue material comprising at least onecellularized amniotic membrane, cellularized chorionic membrane, or acombination thereof; and a nanoparticle composition applied to anoutside surface of the at least one cellularized amniotic membrane,cellularized chorionic membrane, or a combination thereof, wherein theplacental construct is formulated as a single layer graft or multi-layergraft, and wherein the nanoparticle composition includes one or moreelemental ion nanoparticles, one or more elemental nanoparticles, or oneor more impurities.
 2. The placental construct of claim 1, wherein thenanoparticle composition includes one or more elemental ionnanoparticles selected from the group consisting of silver, gold,magnesium, copper, aluminum, titanium, indium, cobalt, nickel, silicon,zirconium, samarium, lanthanum, and zinc.
 3. The placental construct ofclaim 1, wherein the nanoparticle composition includes one or moreelemental nanoparticles selected from the group consisting of silver,gold, magnesium, copper, aluminum, titanium, indium, cobalt, nickel,silicon, zirconium, samarium, lanthanum, and zinc.
 4. The placentalconstruct of claim 1, wherein the nanoparticle composition may includeone or more impurities selected from the group consisting of osmium,rhenium, rhodium, tin, platinum, lithium, sodium, silver, zinc, silicon,carbon, nitrogen, sulfur, iron, moldybdenum, rubidium, copper, andpotassium.
 5. The placental construct of claim 1, wherein the placentalconstruct exhibits antimicrobial, antiviral, antifungal, angiogenic,neurogenic, collagenic, osteogenic properties, or any combinationthereof.
 6. A method of treating a skin condition or soft tissue defectof the skin comprising: applying an effective amount of the construct ofclaim 1 to the skin condition or soft tissue defect of the skin.
 7. Themethod of claim 6, wherein the skin condition is selected from the groupconsisting of an ischemic wound, scar, traumatic wound, severe burn, andsurgical wound.
 8. The method of claim 6, wherein the skin condition isselected from the group consisting of keratosis, melasma, pruritus,spider veins, lentigo, dermatitis, psoriasis, folliculitis, rosacea,impetigo, erysipelas, erythrasma, and eczema.
 9. A method of treating abone defect comprising administering an effective amount of theplacental construct of claim 1 to the bone defect.
 10. The method ofclaim 9, wherein the placental construct aids in bone regeneration. 11.A method of preventing or killing a pathological infection at a site onor within the body comprising administering an effective amount of theplacental construct of claim 1 to the site.
 12. The method of claim 11,wherein the nanoparticle composition comprises magnesium ions.
 13. A kitcomprising the placental construct of claim
 1. 14. The kit of claim 13,further comprising instructions for use thereof.